NIDA Faculty Interview

Current opinion on cannabis and the opioid crisis

Interview with Dr. Susan Weiss

Dr. Susan Weiss is the Director of the Extramural Research Division at the National Institute on Drug Abuse (NIDA). Dr. Weiss has held several positions at NIDA including the Chief of the Science Policy Branch, Acting Director of NIDA’s Office of Science Policy and Communications, and senior science advisor to the NIDA Director, Dr. Nora Volkow. In these capacities, she has worked to increase scientific communication by bridging the gap between research and policy. In this interview, you will learn about Dr. Weiss’s thoughts on the legality of cannabis and the opioid crisis. Dr. Weiss also highlights major knowledge gaps in this field of research as well as potential future directions for cannabis studies.

What are your thoughts on using cannabis to treat the current opioid epidemic?

“It’s a complicated issue. You have people arguing strongly that cannabis is either driving or abating the opioid crisis. I believe neither of those are true. I think it’s important to understand how cannabis, or parts of the plant, such as cannabidiol (CBD), are medically useful particularly with respect to pain. We have a big problem with pain in this country. Not just because of the opioid crisis, but also because we have many people who have chronic pain that has been, and is still being, insufficiently treated. Thus, if there is any possibility that the cannabinoid system could be exploited to help develop new or better pain medications, then I am certainly all for it. However, we need to know more about it. There are a lot of people saying that they are using cannabis to get off of opioids, or to lower their opioid dosage. But, right now it’s mostly anecdote, and we don’t really know if it’s true. There was one recent study that looked prospectively at people who were using opioids and cannabis for pain, and it found the opposite — people who were using both had more pain, and were not reducing their opioid intake. This was an observational study so it’s possible that the people who were using both just had the most severe problems to begin with. It would be great if we could take advantage of what is already happening in the states to learn how people are using marijuana for pain—what products, what doses, and for what types of pain, but right now we have anecdote. States are also considering adding opioid use disorders as an indication for marijuana. In my opinion, this is very dangerous. There is a hint from animal research and from a human laboratory study that CBD may have a role in treating opioid use disorders, but currently the data are sparse, and we already have effective treatments that are underutilized (e.g., methadone, buprenorphine, vivitrol.” (Click here to read more about this topic https://www.liebertpub.com/doi/10.1089/can.2018.29011.rtl)

What are your thoughts on the large market for cannabidiol (CBD)?

“CBD seems to be the new “it” drug. I was even reading how it can be sprinkled on foods to help people get full faster. It is a very interesting constituent of the cannabis plant. But here is the issue: the products that are being sold as CBD are, for the most part, unregulated. So, people buying CBD from grocery stores or over the internet don’t necessarily know what they’re getting. And they are using CBD for all sorts of conditions that we have almost no research on. There is one exception to this, however, Epidiolex® which just recently got Food and Drug Administration (FDA) approval to treat certain forms of severe epilepsy. In addition to the lack of quality control over many of the available CBD products, the other risk comes for using it to treat a condition that already has an FDA-approved treatment, which is known to be effective. While current research indicates that CBD is not addictive, and is probably much less toxic than THC, we don’t know much more about what it can or cannot be used for.”

Is it possible to reschedule cannabis just for scientific researchers?

“We would love to see that happen and it is something that Dr. Nora Volkow has mentioned in testimony before Congress. The Schedule I designation can add costs and delays for people wanting to do research on these substances. This is important not only for marijuana, but also other Schedule I substances. For example, some of the fentanyl analogs could turn out to be antidotes to overdose, or could be developed as treatments for opioid use disorder. Obviously, fentanyl analogues can also be extremely dangerous, but having a research exception to ease the burden for researchers could be very helpful. As scientists, we are very anxious to obtain critical information about these and other Schedule I compounds – either related to their abuse potential or therapeutic applications.”

What is Congress’s argument against enacting new scheduling laws?

“Congress is not arguing against it. I think Congress has been trying to come up with laws that would allow this while balancing public health concerns. Right now, scheduling decisions lie with the Drug Enforcement Administration (DEA). The FDA and NIDA provide scientific input to the DEA on compounds that are being considered for scheduling. The DEA has been trying to make the process of getting a Schedule I license easier for researchers and they have had some success in this area. But for academic researchers who are new to this field, it can still be a daunting task. At a recent meeting I attended, a PI from Colorado described the process she went through to start a project funded by the State. It took her two and a half years because of the security needs, required construction to comply with Colorado smoke-free air laws, and DEA requirements. Yet, she persisted and is now doing the research. You can imagine that many, especially younger scientists, would give up and choose another line of research. So, we are trying to work with our colleagues in the DEA to ease some of these burdens, but currently, they can be a big disincentive.” (Click here to see more about Dr. Emily Lindley’s project at the University of Colorado – Anschutz http://www.ucdenver.edu/research/CCTSI/news-events/newsletter/Pages/-Pioneering-cannabis-studies-(finally)-ready-to-launch.aspx)

Is it more difficult to get a license for clinical research than pre-clinical research?

“The Schedule I registration is similar for both, although some Institutions require an MD to be the Schedule I license holder for a clinical study. But, a separate issue that makes clinical research with cannabis difficult, is that currently the only DEA authorized grower of marijuana for research is the University of Mississippi, under a contract with NIDA. In recent years, we have expanded and diversified the products that are available for research, including varying the levels of THC and CBD and the ratio of the two, but we are still limited compared to what is available in the states. For human clinical trials, products must meet GMP (good manufacturing process) standards. The University of Mississippi has limited supplies of cannabis extracts and other formulations of cannabis for human testing. Another caveat is that a researcher trying to get FDA approval for the cannabis plant as a medication using the NIDA marijuana would have to demonstrate that they could produce an equivalent product when it is ready to be marketed, since NIDA is not a drug manufacturer. That is yet another burden for researchers.”

What is holding research back from getting extracts similar to the ones in the dispensaries?

“For NIDA, it is at least partially a cost issue. The funds to support the contract are the same funds we use to support research. Another variable is time—while we try to meet requests that we receive from researchers, this may involve additional growing, which takes time. In 2016, the DEA stated that they would license other growers and we are looking forward to that occurring. If that happens, it should allow for greater diversity of marijuana products facilitating research on both the medicinal properties of cannabis or its constituents, and the public health impact, especially of the high potency products that many people are using.”

What is stopping companies from selling a packaged pill of the perfect THC:CBD ratio that is the most medicinally beneficial and least addictive?

“The biggest part of that problem is that we don’t know what that ratio is, and it will likely differ for different conditions. Sativex® is half THC and half CBD and has gotten approval in a number of different countries for treating spasms associated with multiple sclerosis and cancer pain. GW Pharma, the company that makes Sativex, was going through the FDA approval process for Sativex as a treatment for severe cancer pain, but they did not meet their expected endpoints. So, we don’t know the magic ratio. Regarding packaging cannabis as a pill, there already are several FDA approved medications that contain synthetic THC (or a similar substance) but they are not very popular. It may be because of the pharmacokinetics of an oral medication, which is very different from that of smoked cannabis. Synthetic THC (Marinol®) has been around since the 80’s. Thus, we still don’t know what the best ratio is, or whether there is an “entourage” effect that emerges when you use the entire plant. It keeps coming back to the fact that we need the research, the research is hard to do, and policies are way ahead of what we know from the research–which is a dangerous combination in my opinion.”

What are your thoughts on the recent IMAGEN study in which acute exposure affected grey matter?

“The changes in grey matter volume were in brain regions with high concentrations of cannabinoid receptors (which is what you might expect). We don’t know what these changes in grey matter mean right now, but just the fact that you could see them with only one or two exposures to cannabis was shocking and concerning.” (Click here for more info on Hugh Garavan’s Study http://www.jneurosci.org/content/early/2019/01/14/JNEUROSCI.3375-17.2018)

What do you think would be the best next studies to further understand the effects of cannabis on the brain?

“This is a very hard question to answer. I think it depends on what you are interested in understanding. If you are interested in the harmful effects, then prenatal exposure is very important to better characterize. We already have concerns about adolescent brain development because we know that the endocannabinoid system plays an important role is neurodevelopment. We are currently engaged in a large prospective study of adolescents (ABCD) that will specifically investigate these effects, and hope to start a similar project beginning at birth and continuing until childhood. From a public health standpoint, we need to know more about the high potency THC products that are gaining in popularity. Conversely, if you are trying to look at the potential therapeutic effects, then we need to have some well-designed controlled trials for various cannabis products or constituents, including CBD. We need to know what works for pain; how well it works; are there specific types of pain cannabinoids work best for; and whether or not tolerance develops with repeated exposure. There is a huge need for this as I previously mentioned.”

What about all of the people who were smoking during pregnancy in the 60’s and 70’s? Or even before then?

“There are a couple of cohort studies that looked at cannabis exposure during that time frame, but it is hard to disentangle the effects, especially since many were polydrug users—that is, they may also have been drinking alcohol and smoking cigarettes. That is why it has been difficult to make clear statements. Still, from the studies that have been done – one in Ottawa, and one in Pittsburg, they found similar outcomes, involving irritability and excitability in infants; effects on executive function later on; and early use of substances. The effects were modest but consistent in two very different groups of exposed children. Also, since these studies began in the 1970s, they involved products with much lower THC levels than what is available now. A more recent study in the Netherlands may be more relevant—they are also seeing differences in brain development and externalizing behaviors as these children are now in school. These studies are difficult to do, but there are more people using cannabis during pregnancy now, including some who think it is safe to use and would not use other substances. Thus, we will start to learn what the effects are of both pre- and perinatal cannabis exposure.”

Message to postbacs:
I proposed the idea that the newsletter should include interviews from scientists that were titans in the field of addiction to serve as an informative reference for all of the postbacs to benefit from. This can be a written record that exposes you to career and personal advice from successful PI’s.
-Holly Hake

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